Neural indices of heritable impulsivity: Impact of the COMT Val158Met polymorphism on frontal beta power during early motor preparation.

Studies of COMT Val158Met suggest that the neural circuitry subserving inhibitory control may be modulated by this functional polymorphism altering cortical dopamine availability, thus giving rise to heritable differences in behaviors. Using an anatomically-constrained magnetoencephalography method and stratifying the sample by COMT genotype, from a larger sample of 153 subjects, we examined the spatial and temporal dynamics of beta oscillations during motor execution and inhibition in 21 healthy Met158/Met158 (high dopamine) or 21 Val158/Val158 (low dopamine) genotype individuals during a Go/NoGo paradigm. While task performance was unaffected, Met158 homozygotes demonstrated an overall increase in beta power across regions essential for inhibitory control during early motor preparation (∼100 ms latency), suggestive of a global motor "pause" on behavior. This increase was especially evident on Go trials with slow response speed and was absent during inhibition failures. Such a pause could underlie the tendency of Met158 allele carriers to be more cautious and inhibited. In contrast, Val158 homozygotes exhibited a beta drop during early motor preparation, indicative of high response readiness. This decrease was associated with measures of behavioral disinhibition and consistent with greater extraversion and impulsivity observed in Val homozygotes. These results provide mechanistic insight into genetically-determined interindividual differences of inhibitory control with higher cortical dopamine associated with momentary response hesitation, and lower dopamine leading to motor impulsivity.

The "when" and "where" of the interplay between attentional capture and response inhibition during a Go/NoGo variant.

Inhibitory control relies on attention, inhibition, and other functions that are integrated across neural networks in an interactive manner. Functional MRI studies have provided excellent spatial mapping of the involved regions. However, finer temporal resolution is needed to capture the underlying neural dynamics and the pattern of their functional contributions. Here, we used anatomically-constrained magnetoencephalography (aMEG) which combines MEG with structural MRI to examine how the spatial ("where") and temporal ("when") processing stages and interregional co-oscillations unfold in real time to contribute to inhibitory control. Healthy participants completed a modified Go/NoGo paradigm in which a subset of stimuli was modified to be visually salient (SAL). Compared to the non-modified condition, the SAL manipulation facilitated response withholding on NoGo trials and hindered responding to Go stimuli, reflecting attentional capture effectuated by an orienting response to SAL stimuli. aMEG source estimates indicate SAL stimuli elicited the attentional "circuit breaker" effect through early activity within a right-lateralized network centered around the lateral temporal cortex with additional activity in the pre-supplementary motor area (preSMA) and anterior insula (aINS/FO). Activity of the bilateral inferior frontal cortex responded specifically to inhibitory demands and was generally unaffected by the attentional manipulation. In contrast, early aINS/FO activity was sensitive to stimulus salience while subsequent activity was specific to inhibitory control. Activity estimated to the medial prefrontal cortex including the dorsal anterior cingulate cortex and preSMA reflected an integrative role that was sensitive to both inhibitory and attentional stimulus properties. At the level of neurofunctional networks, neural synchrony in the theta band (4-7 Hz) revealed interactions between principal cortical regions subserving attentional and inhibitory processes. Together, these results underscore the dynamic, integrative processing stages underlying inhibitory control.

MEG Theta during Lexico-Semantic and Executive Processing Is Altered in High-Functioning Adolescents with Autism.

Neuroimaging studies have revealed atypical activation during language and executive tasks in individuals with autism spectrum disorders (ASD). However, the spatiotemporal stages of processing associated with these dysfunctions remain poorly understood. Using an anatomically constrained magnetoencephalography approach, we examined event-related theta oscillations during a double-duty lexical decision task that combined demands on lexico-semantic processing and executive functions. Relative to typically developing peers, high-functioning adolescents with ASD had lower performance accuracy on trials engaging selective semantic retrieval and cognitive control. They showed an early overall theta increase in the left fusiform cortex followed by greater activity in the left-lateralized temporal (starting at ~250 ms) and frontal cortical areas (after ~450 ms) known to contribute to language processing. During response preparation and execution, the ASD group exhibited elevated theta in the anterior cingulate cortex, indicative of greater engagement of cognitive control. Simultaneously increased activity in the ipsilateral motor cortex may reflect a less lateralized and suboptimally organized motor circuitry. Spanning early sensory-specific and late response selection stages, the higher event-related theta responsivity in ASD may indicate compensatory recruitment to offset inefficient lexico-semantic retrieval under cognitively demanding conditions. Together, these findings provide further support for atypical language and executive functions in high-functioning ASD.

Disruption of Frontal Lobe Neural Synchrony During Cognitive Control by Alcohol Intoxication.

Decision making relies on dynamic interactions of distributed, primarily frontal brain regions. Extensive evidence from functional magnetic resonance imaging (fMRI) studies indicates that the anterior cingulate (ACC) and the lateral prefrontal cortices (latPFC) are essential nodes subserving cognitive control. However, because of its limited temporal resolution, fMRI cannot accurately reflect the timing and nature of their presumed interplay. The present study combines distributed source modeling of the temporally precise magnetoencephalography (MEG) signal with structural MRI in the form of "brain movies" to: (1) estimate the cortical areas involved in cognitive control ("where"), (2) characterize their temporal sequence ("when"), and (3) quantify the oscillatory dynamics of their neural interactions in real time. Stroop interference was associated with greater event-related theta (4 - 7 Hz) power in the ACC during conflict detection followed by sustained sensitivity to cognitive demands in the ACC and latPFC during integration and response preparation. A phase-locking analysis revealed co-oscillatory interactions between these areas indicating their increased neural synchrony in theta band during conflict-inducing incongruous trials. These results confirm that theta oscillations are fundamental to long-range synchronization needed for integrating top-down influences during cognitive control. MEG reflects neural activity directly, which makes it suitable for pharmacological manipulations in contrast to fMRI that is sensitive to vasoactive confounds. In the present study, healthy social drinkers were given a moderate alcohol dose and placebo in a within-subject design. Acute intoxication attenuated theta power to Stroop conflict and dysregulated co-oscillations between the ACC and latPFC, confirming that alcohol is detrimental to neural synchrony subserving cognitive control. It interferes with goal-directed behavior that may result in deficient self-control, contributing to compulsive drinking. In sum, this method can provide insight into real-time interactions during cognitive processing and can characterize the selective sensitivity to pharmacological challenge across relevant neural networks.

When the brain changes its mind: Oscillatory dynamics of conflict processing and response switching in a flanker task during alcohol challenge.

Despite the subjective experience of being in full and deliberate control of our actions, our daily routines rely on a continuous and interactive engagement of sensory evaluation and response preparation streams. They unfold automatically and unconsciously and are seamlessly integrated with cognitive control which is mobilized by stimuli that evoke ambiguity or response conflict. Methods with high spatio-temporal sensitivity are needed to provide insight into the interplay between automatic and controlled processing. This study used anatomically-constrained MEG to examine the underlying neural dynamics in a flanker task that manipulated S-R incongruity at the stimulus (SI) and response levels (RI). Though irrelevant, flankers evoked automatic preparation of motor plans which had to be suppressed and reversed following the target presentation on RI trials. Event-related source power estimates in beta (15-25 Hz) frequency band in the sensorimotor cortex tracked motor preparation and response in real time and revealed switching from the incorrectly-primed to the correctly-responding hemisphere. In contrast, theta oscillations (4-7 Hz) were sensitive to the levels of incongruity as the medial and ventrolateral frontal cortices were especially activated by response conflict. These two areas are key to cognitive control and their integrated contributions to response inhibition and switching were revealed by phase-locked co-oscillations. These processes were pharmacologically manipulated with a moderate alcohol beverage or a placebo administered to healthy social drinkers. Alcohol selectively decreased accuracy to response conflict. It strongly attenuated theta oscillations during decision making and partly re-sculpted relative contributions of the frontal network without affecting the motor switching process subserved by beta band. Our results indicate that motor preparation is initiated automatically even when counterproductive but that it is monitored and regulated by the prefrontal cognitive control processes under conflict. They further confirm that the regulative top-down functions are particularly vulnerable to alcohol intoxication.

Behavioral and Brain Activity Indices of Cognitive Control Deficits in Binge Drinkers.

Heavy episodic drinking is prevalent among young adults and is a public issue of increasing importance. Its initiation and maintenance are associated with deficits in the capacity to inhibit automatic processing in favor of non-habitual responses. This study used functional magnetic resonance imaging (fMRI) to examine behavioral and brain activity indices of cognitive control during the Stroop task as a function of binge drinking. Heavy episodic drinkers (HED) reported consuming 5+/6+ drinks in two hours at least five times in the past six months and were compared to light drinkers (LED) who reported two or fewer binge episodes but were matched on demographics, intelligence and family history of alcoholism. Greater conflict-induced activity in the ventrolateral prefrontal cortex (VLPFC) and thalamus was observed in HED participants and it was positively correlated with alcohol intake and alcohol-related harmful consequences. HEDs maintained intact accuracy but at a cost of prolonged reaction times to high-conflict trials and increased ratings of task difficulty. Greater activation of the areas implicated in cognitive control is consistent with compensatory network expansion to meet higher cognitive demands. These results provide further insight into degradation of cognitive control in HEDs which may benefit development of detection and prevention strategies.